OP0218 INCIDENT MALIGNANCIES IN PATIENTS WITH RHEUMATOID ARTHRITIS IN DAILY RHEUMATOLOGICAL CARE
Authors: M. Schaefer, Y. Meissner, B. Manger, S. Berger, K. Rockwitz, A. Regierer, A. Strangfeld
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Based on results of the post-authorisation safety trial Oral Surveillance (OS, see [1]), the European and US-American regulatory agencies in 2021 issued warnings about malignancy risk associated with the Janus kinase inhibitor (JAKi) tofacitinib and required changes in labelling. <h3>Objectives</h3> To analyse incident malignancies under treatment with JAKi, tumor necrosis factor inhibitors (TNFi), abatacept (ABA), rituximab (RTX), interleukin 6 inhibitors (IL6i) or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs - bionaive) in patients with rheumatoid arthritis (RA) observed in daily rheumatological care. <h3>Methods</h3> Data from patients without cancer history from the biologics register RABBIT were included with treatment episodes started 01/2017 - 04/2022. Incidence rates (IR) of malignancies (without non melanoma skin cancer, NMSC) per 1000 patient-years (PY) with 95% confidence intervals (CI) and adjusted hazard ratios (HR) were calculated for all and selected patients according to OS inclusion criteria (age ≥ 50 years and ≥ 1 cardiovascular (CV) risk factor) to compare treatment groups to TNFi. Andersen-Gill regression analysis was used with a 6-month risk window, adjusted via stabilized and winsorized inverse probability of treatment weights taking into account age, sex, smoking, disease activity, prior therapies, comorbidities, and type of enrolling institution (clinic vs. private practice) as covariates. Multiple imputation of missing data was applied. <h3>Results</h3> 2763 JAKi, 3403 TNFi, 744 ABA, 834 RTX, 1125 IL6i and 1130 csDMARD initiations were documented. Patients with a JAKi start were less often men and (except RTX patients) slightly older and had a longer RA disease duration (Table 1). The seropositive proportion and the number of prior treatments with biological (b) or targeted (ts) synthetic DMARDs was higher than in TNFi and csDMARD groups, but lower than in ABA and RTX groups. 151 incident malignancies were reported. Across treatments, patients showed comparable IRs between 7 and 11 events per 1000 PY. Among selected patients IRs were higher (13.2 events per 1000 PY in JAKi patients, 95% CI: 9.5 – 17.9). In adjusted analyses, neither JAKi (HR 1.06, 95% CI: 0.70 - 1.61), ABA (HR 0.73, 0.38 - 1.40), RTX (HR 0.86, 0.42 - 1.75), IL6i (HR 0.79, 0.45 - 1.40) nor csDMARDs (HR 2.07, 0.87 - 4.94) showed a significantly altered risk for malignancies compared with TNFi in unselected patients, with similar results in selected patients. <h3>Conclusion</h3> IR of malignancies in selected patients receiving JAKi in a real-world setting was numerically higher than reported for tofacitinib in OS. However, we found no statistical evidence of an increased malignancy risk with JAKi compared to TNFi, although patients on JAKi were older and had longer disease duration and more previous b/tsDMARDs treatments. Further analyses assessing exposure in terms of treatment duration are needed. <h3>Reference</h3> [1]PMID: 35081280 <h3>Acknowledgements</h3> RABBIT is currently supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Galapagos, Hexal, Lilly, MSD, Pfizer, Samsung Bioepis, Sanofi Aventis, VIATRIS SANTE and UCB. <h3>Disclosure of Interests</h3> Martin Schaefer Grant/research support from: Non-personal, joint grant from a consortium of 14 pharmaceutical companies (AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Galapagos, Hexal, Lilly, MSD, Pfizer, Samsung Bioepis, Sanofi Aventis, VIATRIS SANTE and UCB) for the biologics register RABBIT to my institute, Yvette Meissner Speakers bureau: Pfizer, Grant/research support from: Non-personal, joint grant from a consortium of 14 pharmaceutical companies (AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Galapagos, Hexal, Lilly, MSD, Pfizer, Samsung Bioepis, Sanofi Aventis, VIATRIS SANTE and UCB) for the biologics register RABBIT to my institute, Bernhard Manger Speakers bureau: AbbVie, Alexion, EUSA, Cellgene, Gilead, Janssen, Lilly, MSD, Pfizer, Roche, Sanofi-Genzyme, Consultant of: EUSA, MSD, Vifor, Sylvia Berger: None declared, Karin Rockwitz: None declared, Anne Regierer Speakers bureau: BMS, Novartis, Pfizer, Roche, Grant/research support from: joint unconditional grant from: AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB and Viatris, Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB, Grant/research support from: Non-personal, joint grant from a consortium of 14 pharmaceutical companies (AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Galapagos, Hexal, Lilly, MSD, Pfizer, Samsung Bioepis, Sanofi Aventis, VIATRIS SANTE and UCB) for the biologics register RABBIT to my institute.